Zhaohui Ni

Diagnostic Value of Urinary Kidney Injury Molecule 1 for Acute Kidney Injury: A Meta-Analysis

Background Urinary Kidney Injury Molecule 1 (KIM-1) is a proximal tubular injury biomarker for early detection of acute kidney injury (AKI), with variable performance characteristics depending on clinical and population settings. Methods Meta-analysis was performed to assess the diagnostic value of urinary KIM-1 in AKI. Relevant studies were searched from MEDLINE, EMBASE, Pubmed, Elsevier Science Direct, Scopus, Web of Science, Google Scholar and Cochrane Library. Meta-analysis methods were used to pool sensitivity and specificity and to construct summary receiver operating characteristic (SROC) curves. Results A total of 2979 patients from 11 eligible studies were enrolled in the analysis. Five prospective cohorts, two cross-sectional and four case-control studies were identified for meta-analysis. The estimated sensitivity of urinary KIM-1 for the diagnosis of AKI was 74.0% (95% CI, 61.0%–84.0%), and specificity was 86.0% (95% CI, 74.0%–93.0%). The SROC analysis showed an area under the curve of 0.86(0.83–0.89). Subgroup analysis suggested that population settings and detection time were the key factors affecting the efficiency of KIM-1 for AKI diagnosis. Limitation Various population settings, different definition of AKI and Serum creatinine level used as the standard might have influence on AKI diagnosis. The relatively small number of studies and heterogeneity between them also affected the evaluation. Conclusion Urinary KIM-1 may be a promising biomarker for early detection of AKI with considerable predictive value, especially for cardiac surgery patients, and its potential value needs to be validated in large studies and across a broader scope of clinical settings.

A multicenter application and evaluation of the oxford classification of IgA nephropathy in adult chinese patients.

BACKGROUND The Oxford classification of immunoglobulin A (IgA) nephropathy (IgAN) provides a histopathologic grading system that is associated with kidney disease outcomes independent of clinical features. We evaluated the Oxford IgAN classification in a large cohort of patients from China. STUDY DESIGN Retrospective study. SETTING & PARTICIPANTS 1,026 adults with IgAN from 18 referral centers in China. Inclusion criteria and statistical analysis were similar to the Oxford study. PREDICTORS Histologic findings of mesangial hypercellularity score, endocapillary proliferation, segmental sclerosis or adhesion, crescents, necrosis, and tubular atrophy/interstitial fibrosis. Clinical features, blood pressure, estimated glomerular filtration rate (eGFR), proteinuria, and treatment modalities. OUTCOMES Time to a 50% reduction in eGFR or end-stage renal disease (the combined event); the rate of eGFR decline (slope of eGFR); proteinuria during follow-up. RESULTS Compared with the Oxford cohort, the Chinese cohort had a lower proportion of patients with mesangial hypercellularity (43%) and endocapillary proliferation (11%), higher proportion with segmental sclerosis or adhesion (83%) and necrosis (15%), and similar proportion with crescents (48%) and tubular atrophy/interstitial fibrosis (moderate, 24%; severe, 3.3%). During a median follow-up of 53 (25th-75th percentile, 36-67) months, 159 (15.5%) patients reached the combined event. Our study showed that patients with a mesangial hypercellularity score higher than 0.5 were associated with a 2.0-fold (95% CI, 1.5-2.8; P<0.001) higher risk of the combined event than patients with a score of 0.5 or lower. Patients with tubular atrophy/interstitial fibrosis of 25%-50% and >50% versus <25% were associated with a 3.7-fold (95% CI, 2.6-5.1; P<0.001) and 15.1-fold (95% CI, 9.5-24.2; P<0.001) higher risk of the combined event, respectively. Endocapillary proliferation, glomerular crescents, and necrosis were not significant. LIMITATIONS Retrospective study; the therapeutic interventions were miscellaneous. CONCLUSIONS We confirmed the associations of mesangial hypercellularity and tubular atrophy/interstitial fibrosis with kidney disease outcomes.

Clinical usefulness of novel biomarkers for the detection of acute kidney injury following elective cardiac surgery.

Background/Aims: Acute kidney injury (AKI) is common following cardiac surgery and predicts a poor outcome. However, the early detection of AKI has proved elusive and most cases are diagnosed only following a significant rise in serum creatinine (SCr). We compared a panel of early biomarkers of AKI for the detection of AKI in patients undergoing heart surgery. This study included serum cystatin C (CyC) and urinary levels of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), retinol-binding protein (RBP) and N-acetyl-β-D-glucosaminidase (NAG). Methods: We retrospectively identified 15 patients undergoing open cardiac surgery who developed AKI within 72 h postoperatively. For these, we identified 15 matched controls also having undergone surgery but without AKI. Serial serum and urine samples had prospectively been postoperatively obtained from all patients at 0, 2, 4, 6, 10, 24, 48 and 72 h after admission to the intensive care unit. AKI was defined as a >50% increase in SCr. CyC was measured by nephelometry, while NGAL, IL-18, and RBP were measured by ELISA and NAG was measured by spectrophotometry. The urinary biomarkers were normalized to urinary creatinine (UCr) concentration. Each marker was assessed at each time point for its predictive value using receiver operating characteristic curves to predict AKI. Results: Following the exclusion of 1 case due to a urinary tract infection, the final cohort consisted of 29 patients aged 62.9 ± 13.7 years with baseline SCr of 73.2 ± 11.9 µmol/l. While there were no differences in the demographics between cases and controls, the aortic clamp time was predictably higher in AKI cases than in controls (60.6 ± 13.9 vs. 43.0 ± 9.2 min, p < 0.05). Each biomarker differed significantly between cases and controls for at least one time point. The optimal area under the curve (AUC) was for CyC at 10 h (sensitivity 0.71, specificity 0.92, cutoff 1.31 mg/l), NGAL at 0 h (sensitivity 0.84, specificity 0.80, cutoff 49.15 µg/g UCr), IL-18 at 2 h (sensitivity 0.85, specificity 0.73, cutoff 285.65 ng/g UCr), RBP at 0 h (sensitivity 0.75, specificity 0.67, cutoff 2,934.65 µg/g UCr) and NAG at 4 h (sensitivity 0.86, specificity 0.67, cutoff 37.05 U/mg UCr). Using a combination of all 5 biomarkers analyzed at the optimal time point as above, we were able to obtain an AUC of 0.98 (0.93–1.02, p < 0.001) in this limited sample. Conclusion: The use of serum and urinary biomarkers for the prediction of AKI in patients undergoing cardiac surgery is highly dependent on the sampling time. Of the evaluated markers urinary NGAL had the best predictive profile. The previously unstudied marker of urinary RBP showed similar predictive power as more established markers. By combining all 5 studied biomarkers we were able to predict significantly more cases, suggesting that the use of more than one marker may be beneficial clinically.

Strong Impact of Acute Kidney Injury on Survival After Liver Transplantation

Acute kidney injury (AKI) is a major complication in orthotopic liver transplantation (OLT). In an evaluation of Acute Kidney Injury Network (AKIN) criteria in liver transplanted patients, we retrospectively analyzed the usefulness of these criteria to predict survival of 193 consecutive patients at a single center who underwent primary OLT for clinical parameters and peak AKI. Postoperative AKI according to AKIN occurred in 60.1% of the patients, namely, stages 1, 2, and 3 in 30%, 13% and 17.1% respectively. Using multivariate logistic regression, AKIN stage 1 and 2 AKI were independently associated with the pre-OLT Model for End-Stage Liver Disease (MELD) score and age, while stage 3 AKI was independently associated with MELD and Acute Physiology and Chronic Health Evaluation (APACHE) II scores. The 28-day and 1-year mortality post-OLT of AKI patients were 15.5% and 25.9% respectively compared with 0% and 3.9% among non-AKI patients (P < .05 for both). The survival rates of non-AKI and stages 1, 2, and 3 AKI subjects were 96%, 85.5%, 84%, and 45.3%, respectively. Cox regression analysis showed independent risk factors for mortality during the first year after transplantation to include post-OLT AKI (12.1; P < .05), post-OLT infection (HR 4.7; P < .01), pre-OLT hypertension (HR 4.4; P < .01) hazard ratio [HR] and post-OLT APACHE II ≥10 (HR 3.6; P < .05). We concluded that AKI as defined by the AKIN criteria is a major complication of OLT linked to a poor outcomes. It remains to be evaluated whether aggressive perioperative therapy to prevent AKI can improve survival among OLT patients.

Clinical Outcome of Twice-Weekly Hemodialysis Patients in Shanghai

Background: Twice-weekly hemodialysis (HD) is prevalent in the developing countries and the clinical outcome of this population remains to be elucidated. Methods: Data were collected from Shanghai Renal Registry. 2,572 patients undergoing regular HD in Shanghai on January 2007 were enrolled into the cohort study with 2 years’ follow-up. Clinical and HD parameters obtained from the network were utilized to compare twice-weekly with thrice-weekly HD. Results: Compared with patients on thrice-weekly HD, the twice-weekly HD patients were significantly younger and had significantly longer HD session time, higher single-pool Kt/V (spKt/V) but shorter HD vintage (p < 0.001). Kaplan-Meier survival analysis indicated that the two groups had similar survival. Multivariate Cox regression analysis showed that age, body mass index, serum albumin and weekly Kt/V were predictors of patient mortality. Conclusions: The similar survival between twice-weekly HD and thrice-weekly HD is likely relating to patient selection; dialysis adequacy of twice-weekly HD remains to be elucidated.

Prevalence of non-diabetic renal disease in patients with type 2 diabetes

It is important to differentiate proteinuria from non-diabetic renal diseases (NDRD) or diabetic nephropathy in diabetic patients. The purpose of our study was to evaluate the prevalence of NDRD. A retrospective analysis was performed on diabetic patients who had undergone renal biopsy during a 6-year period. Our study revealed a high prevalence of NDRD in the diabetic population. Sixty-nine patients were investigated, 52.2% were diagnosed as NDRD and 47.8% as DN. Focal segmental glomerulosclerosis was the most common lesion found in patients with NDRD. We found a relationship between DN and fasting blood glucose level, systolic blood pressure, diastolic blood pressure, LVMI, intima-media thickening (IMT), and the presence of carotid plaques. Patients with NDRD had a lower incidence of diabetic retinopathy (DR). The absence of DR to differentiate NDRD had a sensitivity of 72.7%, a specificity 91.7%, and an ROC=0.822. Fasting blood glucose level had a sensitivity and specificity of 93.9% and 75%, respectively. Similarly, the use of IMT had sensitivity and specificity of 90% and 75.8%, respectively. In this study, we determined that the absence of DR, a lower fasting blood glucose level, and IMT is useful in differentiating NDRD from DN in diabetic patients with overt proteinuria.

Circulating levels of asymmetric dimethylarginine are an independent risk factor for left ventricular hypertrophy and predict cardiovascular events in pre-dialysis patients with chronic kidney disease.

BACKGROUND Several studies have related the circulating level of asymmetric dimethylarginine (ADMA) to cardiac remodeling and cardiovascular (CV) events in end-stage renal disease (ESRD) patients. Studies investigating this relationship in patients with pre-dialysis chronic kidney disease (CKD) are lacking. METHODS We enrolled 76 CKD patients (age, 46.7+/-14.3 years, 39 females) and 15 controls (age, 40.1+/-18.5 years, 6 females). Clinical parameters, blood biochemistry and echocardiographic findings were recorded, and plasma ADMA concentrations measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Patients were prospectively followed up for a median of 15 (range, 6-24) months. RESULTS Plasma ADMA was significantly elevated in CKD patients compared with controls (41.56+/-12.76 microg/mL vs 17.12+/-7.09 microg/mL, P<0.001), and correlated with the left ventricular mass index (LVMI) (r=0.597, P<0.001). During follow-up, 25 patients experienced new CV events and their plasma ADMA level was significantly elevated (48.27+/-13.70 vs 34.91+/-6.38 in CV event-free patients, P<0.001). Cox regression analysis further confirmed that ADMA was an independent risk factor for CVD (HR=1.175, 95%CI[1.070-1.290], P=0.001). CONCLUSION Similar to findings in ESRD patients, elevated circulating levels of ADMA may increase the risk of LVH and CV events in pre-dialysis CKD patients.

Astragaloside IV Ameliorates Renal Fibrosis via the Inhibition of Mitogen-Activated Protein Kinases and Antiapoptosis In Vivo and In Vitro

Apoptosis of renal tubular cells plays a crucial role in renal fibrosis. Astragaloside IV (AS-IV), a compound extracted from Radix Astragali, has been shown to inhibit renal tubular cell apoptosis induced by high glucose, but its role in preventing chronic renal fibrosis as well as the underlying molecular mechanisms involved still remain obscure. In this study, human kidney tubular epithelial cells induced by transforming growth factor-β1 (TGF-β1) were used to investigate the protective role of AS-IV in antifibrosis. As an in vivo model, mice subjected to unilateral ureteral obstruction (UUO) were administered AS-IV (20 mg/kg) by intraperitoneal injection for 7 days. AS-IV significantly alleviated renal mass loss and reduced the expression of α-smooth muscle actin, fibronectin, and collagen IV both in vitro and in vivo, suggesting that this compound functions in the inhibition of renal tubulointerstitial fibrosis. Furthermore, transferase-mediated dUTP nick-end labeling assay results both in vivo and in vitro showed that AS-IV significantly attenuated both UUO and TGF-β1–induced cell apoptosis and prevented renal tubular epithelial cell injury in a dose-dependent manner. Western blotting results also revealed that the antiapoptotic effect of AS-IV was reflected in the inhibition of caspase-3 activation, which might be mediated primarily by the downregulation of mitogen-activated protein kinase effectors phospho-p38 and phospho–c-Jun N-terminal kinase. These data infer that AS-IV effectively attenuates the progression of renal fibrosis after UUO injury and may have a promising clinical role as a potential antifibrosis treatment in patients with chronic kidney disease.

Better preservation of residual renal function in peritoneal dialysis patients treated with a low-protein diet supplemented with keto acids: a prospective, randomized trial

BACKGROUND While a low-protein diet may preserve residual renal function (RRF) in chronic kidney disease (CKD) patients before the start of dialysis, a high-protein intake is usually recommended in dialysis patients to prevent protein-energy wasting. Keto acids, which were often recommended to pre-dialysis CKD patients treated with a low-protein diet, had also been reported to be associated with both RRF and nutrition maintenance. We conducted a randomized trial to test whether a low-protein diet with or without keto acids would be safe and associated with a preserved RRF during peritoneal dialysis (PD). METHODS To assess the safety of low protein, we first conducted a nitrogen balance study in 34 incident PD patients randomized to receive in-centre diets containing 1.2, 0.9 or 0.6 g of protein/kg ideal body weight (IBW)/day for 10 days. Second, 60 stable PD patients [RRF 4.04 +/- 2.30 ml/ min/1.73 m(2), urine output 1226 +/- 449 ml/day, aged 53.6 +/- 12.8 years, PD duration 8.8 (1.5-17.8) months] were randomized to receive either a low- (LP: 0.6-0.8 g/kg IBW/day), keto acid-supplemented low- (sLP: 0.6-0.8 g/kg IBW/day with 0.12 g/kg IBW/day of keto acids) or high-protein (HP: 1.0-1.2 g/kg IBW/day) diet. The groups were followed for 1 year and RRF as well as nutritional status was evaluated serially. RESULTS A neutral or positive nitrogen balance was achieved in all three groups. RRF remained stable in group sLP (3.84 +/- 2.17 to 3.39 +/- 3.23 ml/min/1.73 m(2), P = ns) while it decreased in group LP (4.02 +/- 2.49 to 2.29 +/- 1.72 ml/min/1.73 m(2), P < 0.05) and HP (4.25 +/- 2.34 to 2.55 +/- 2.29 ml/min/1.73 m(2), P < 0.05). There was no change from baseline on nutritional status in any of the groups during follow-up. CONCLUSIONS A diet containing 0.6-0.8 g of protein/kg IBW/day is safe and, when combined with keto acids, is associated with an improved preservation of RRF in relatively new PD patients without significant malnutrition or inflammation.

Comparison of peritoneal dialysis practice patterns and outcomes between a Canadian and a Chinese centre

UNLABELLED Objective. We compared patient characteristics, dialysis practice patterns and outcomes of peritoneal dialysis (PD) patients between one Chinese centre and one Canadian centre to determine whether observed differences in demographics and practices are associated with patient and technique survival. METHODS This study included all patients who started on PD between 1 January 2000 and 31 December 2004 at the University Health Network, University of Toronto, Canada and Renji Hospital, Shanghai Jiao Tong University School of Medicine, China. They were followed up from the date of PD initiation until death, cessation of PD, transfer to other centres or to the end of the study (31 December 2006). RESULTS We studied 496 patients, 256 from the Canadian centre and 240 from the Chinese centre. Canadian patients were older and more likely to have diabetes and cardiovascular comorbidities at the initiation of PD, while the Chinese patients had lower residual renal function (RRF). More Canadian patients were treated with APD, whereas all Chinese patients were on CAPD with a lower PD volume. Crude patient survival rates at 1, 2, 3 and 5 years were similar between the two centres: 90%, 79%, 72% and 61% for Canadian and 90%, 79%, 71% and 64% for Chinese patients, respectively. After adjustment for demographic and clinical variables, there is no significant difference in mortality between Chinese patients and Canadian patients. Age, cardiovascular disease, diabetes, RRF and serum albumin were independent predictors of patient survival. The death-censored technique survival rates were significantly lower among the Canadian patients compared to Chinese patients. Chinese patients showed a lower risk of technique failure (HR 0.491, 95% CI 0.269-0.898, P = 0.021) after adjustment for patient characteristics. Chinese centre, BMI, serum albumin and gender were independent predictors of technique survival. The average peritonitis rate was one episode every 36.1 patient-months in Canadian patients and one episode every 60.6 patient-months in their Chinese counterparts. CONCLUSION Patient characteristics, dialysis practice patterns and outcomes vary between Canadian and Chinese patients. The variability in patient outcomes between these two centres indicates that further improvements may be possible in both centres. We have identified several areas for improving outcomes.